Hydriodic acid-mediated cyclization of a-substituted secondary 2-ethenylbenzamides: Synthesis of 2-substituted 2,3-dihydro-3,3-dimethyl-1H- isoindol-1-ones and 3,3-disubstituted (E)-1-(arylimino)-1,3- dihydroisobenzofurans

Article abstract of DOI:10.1002/hlca.201000172

A new and facile method for the preparation of 2-substituted 2,3-dihydro-3,3-dimethyl-1H-isoindol-1-ones 3 and 3,3-disubstituted (E)-1-(arylimino)-1,3-dihydroisobenzofurans 6 has been developed. Thus, treatment of N-alkyl(or aryl)-2-(1-methylethen-1-yl)be

Full text of DOI:10.1002/hlca.201000172

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Hydriodic Acid-Mediated Cyclization of a-Substituted Secondary
2-Ethenylbenzamides: Synthesis of 2-Substituted 2,3-Dihydro-3,3-
dimethyl-1H-isoindol-1-ones and 3,3-Disubstituted (E)-1-(Arylimino)-
1,3-dihydroisobenzofurans
by Kazuhiro Kobayashi*, Seiki Fujita, Daisuke Nakai, Shogo Fukumoto,
Shuhei Fukamachi, and Hisatoshi Konishi
Division of Applied Chemistry, Department of Chemistry and Biotechnology, Graduate School of
Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan
(phone/fax: þ 81-857-315263; e-mail: kkoba@chem.tottori-u.ac.jp)
A new and facile method for the preparation of 2-substituted 2,3-dihydro-3,3-dimethyl-1H-isoindol-
1-ones 3 and 3,3-disubstituted (E)-1-(arylimino)-1,3-dihydroisobenzofurans 6 has been developed. Thus,
treatment of N-alkyl(or aryl)-2-(1-methylethen-1-yl)benzamides 2 with concentrated hydriodic acid
(HI) in MeCN at room temperature afforded 3. Similar treatment of N-aryl-2-(1-phenylethen-1-
yl)benzamide 5 with concentrated HI at 08 afforded 6.
Introduction. – We previously reported a synthesis of 3,3-disubstituted-2,3-dihydro-
1H-isoindol-1-ones based on iodoamination of a-substituted secondary 2-ethenylbenz-
amides, which could be prepared by the reaction of a-substituted 2-lithiostyrenes with
isocyanates [1]. As an extension of this work, we herein describe the results of our study
on HI-mediated cyclization of a-substituted secondary 2-ethenylbenzamides, which
provide concise and efficient synthetic routes to 2-substituted 2,3-dihydro-3,3-
dimethyl-1H-isoindol-1-ones and 3,3-disubstituted (E)-1-(arylimino)-1,3-dihydroiso-
benzofurans depending on the a-substituents of a-substituted secondary 2-ethenyl-
benzamides. The synthesis of 2,3-dihydro-1H-isoindol-1-ones has recently attracted
considerable attention owing to the occurrence of biological active compounds
containing this heterocyclic system [2]. A number of methods for the synthesis of this
system have been developed [3]. However, most of these methods require several steps
and/or involve tedious reaction conditions. On the other hand, a few general methods
have been reported for the preparation of 1-(alkyl(or aryl)imino)-1,3-dihydroisoben-
zofuran derivatives [4]. For example, Kunai and co-workers have reported a synthesis
of 3,3-disubstituted 1-(tert-octylimino)-1,3-dihydroisobenzofurans by three-compo-
nent coupling using arynes and tert-octyl isocyanide [4a][4c]. This class of molecules
may be of biological interest, because a number of molecules, which have a related
isobenzofuran-1(3H)-one (phthalide) structure, have exhibited a variety of biological
activities [5].
Results and Discussion. – 2,3-Dihydro-3,3-dimethyl-1H-isoindol-1-ones 3 were
synthesized from 2-bromo-a-methylstyrenes 1 via N-alkyl(or aryl)-2-(1-methylethen-1-
yl)benzamides 2 as outlined in Scheme 1. The 2-ethenylbenzamides 2 were prepared
ꢀ 2010 Verlag Helvetica Chimica Acta AG, Zꢁrich

Helvetica Chimica Acta – Vol. 93 (2010)
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from the 2-bromostyrenes 1 as described in [1]. Thus, Li/Br exchange between 1 and
BuLi in Et2O at 08 generated the corresponding 2-lithiostyrene derivatives. These were
then allowed to react with isocyanates to afford 2-ethenylbenzamides 2 in moderate-to-
fair yields. First, 2-(1-methylethen-1-yl)-N-phenylbenzamide (2a) was treated with
2 mol-equiv. of HI in MeCN at room temperature to yield the desired 2,3-dihydro-3,3-
1
dimethyl-2-phenyl-1H-isoindol-1-one (3a) in fair yield. The IR and H-NMR spectra
were identical to those reported in [1]. The use of less than 2 mol-equiv. of HI gave
decreased yields of the desired product. Conversion of the other 2-(1-methylethen-1-
yl)benzamides 2b – 2e to the 2,3-dihydro-1H-isoindol-1-ones 3b – 3e, respectively, was
performed under the same conditions in comparable yields. These results are
summarized in Table 1.
Scheme 1
Table 1. Preparation of 2,3-Dihydro-1H-isoindol-1-ones 3 from 1 via 2
Entry
Starting material
R3
Intermediate
Yielda) [%]
Product
Yielda) [%]
1
2
3
4
5
1a
1a
1b
1b
1c
Ph
2a
2b
2c
2d
2e
65
58
59
64
60
3a
3b
3c
3d
3e
72
69
62
69
70
4-ClꢀC6H4
Ph
t-Bu
Ph
a) Yields of isolated products.
Subsequently, we investigated the cyclization of N-aryl-2-(1-arylethen-1-yl)benz-
amides 5, which can also be prepared by reacting 2-lithio-a-arylstyrenes, generated
from 2-bromo-a-arylstyrenes 4 and BuLi, with aryl isocyanates, as illustrated in
Scheme 2. The yields of 4 are summarized in Table 2, which indicates that they are
moderate-to-fair. First, we examined the reaction of N-phenyl-2-(1-phenylethen-1-
yl)benzamide (5a) with concentrated HI under similar conditions as described for the
preparation of 2,3-dihydro-1H-isoindol-1-ones 3 (Scheme 2). The reaction was
complete at 08 in 1 h, and the precipitated product was collected. However, we found
1
that the spectroscopic data (IR and H-NMR) of this product were not identical to
those of previously prepared 2,3-dihydro-3-methyl-2,3-diphenyl-1H-isoindol-1-one [1].
We determined the structure of this product to be (E)-1,3-dihydro-3-methyl-3-phenyl-
1-(phenylimino)isobenzofuran (6a) on the basis of its spectroscopic data and elemental
analysis (see Exper. Part). The signal assignable to HꢀC(7) appears at considerable
lowfield (d(H) 9.98), probably due to the deshielding effect of the benzene ring of the
1-phenylimino group. The (E)-configuration was unambiguously determined by NOE

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Helvetica Chimica Acta – Vol. 93 (2010)
experiments. Thus, irradiation of the signal at d(H) 9.98 assignable to HꢀC(7) resulted
in an enhancement (15%) of the signal at d(H) 8.08 assignable to ortho-H-atoms of the
benzene ring of the 1-phenylimino group. Similar treatment of the other N-aryl-2-(1-
arylethen-1-yl)benzamides 5b – 5f led to the formation of the 3,3-disubstituted (E)-2-
(arylimino)-1,3-isobenzofurans 6b – 6f, respectively. The yields of the products are also
listed in Table 2 which indicates that good yields are generally realized, while N-phenyl-
2-(2-phenyl-3-methylethen-1-yl)benzamide (5f) gave the corresponding desired prod-
uct 6f in somewhat lower yield (Entry 6). The b-Me group of the vinyl moiety may
render this cyclization difficult. The formation of the dihydro-imino-isobenzofuran
structure is ascribed to the steric hindrance due to two aryl groups of the 2,3-diaryl-2,3-
dihydro-1H-isoindol-1-one structure.
Scheme 2
Table 2. Preparation of (E)-1-(Arylimino)-2,3-dihydroisobenzofurans 6 from 4 via 5
Entry
Starting material
Ar2
Intermediate
Yielda) [%]
6
Yielda) [%]
1
2
3
4
5
6
4a
4a
4a
4b
4c
4d
Ph
5a
5b
5c
5d
5e
5f
53
63
62
55
59
51
6a
6b
6c
6d
6e
6f
86
93
89
88
80
66
4-ClꢀC6H4
4-BrꢀC6H4
4-ClꢀC6H4
Ph
Ph
a) Yields of isolated products.
The 1,3-dihydro-1-iminoisobenzofuran structure was further confirmed by con-
verting 6a to 3-methyl-3-phenylisobenzofuran-1(3H)-one (7) by acid hydrolysis, as
shown in Scheme 3.
Scheme 3

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1277
In conclusion, the results mentioned above demonstrate that 2-substituted 2,3-
dihydro-3,3-dimethyl-1H-isoindol-1-one and 3,3-disubstituted (E)-1-(arylimino)-1,3-
dihydroisobenzofurans can be prepared from a-substituted 2-bromostyrenes and
isocyanates. The method should be useful in the synthesis of these classes of
heterocyclic compounds, because the starting materials are readily available, and the
operations are very simple.
Experimental Part
General. All of the org. solvents used in this study were dried over appropriate drying agents and
distilled prior to use. TLC: Kieselgel 60 PF254 (Merck). Column chromatography (CC): Kieselgel 60
(0.063 – 0.200 mm; Merck). M.p.: Laboratory Devices MEL-TEMP II; uncorrected. IR Spectra:
.
Shimadzu FTIR-8300 spectrophotometer; ˜n in cmꢀ1 1H-NMR Spectra: JEOL ECP500 FT NMR
spectrometer at 500 MHz or JEOL LA400 FT NMR spectrometer at 400 MHz in CDCl3; d in ppm rel. to
Me4Si as internal standard, J in Hz. 13C-NMR Spectra: JEOL ECP500 FT NMR spectrometer at
125 MHz; d in ppm rel. to Me4Si as internal standard. LR-EI-MS: JEOL JMS AX505 HA spectrometer
at 70 eV; in m/z (rel. %).
a-Substituted 2-Bromostyrenes 1a [6], 1b [7], 1c [7], 4a [8], 4b [9], 4c [10], and 4d [11] were prepared
by the appropriate reported methods. All other chemicals used in this study were commercially available.
a-Substituted 2-Ethenylbenzamides 2 and 5. These compounds were prepared by reacting a-
substituted 2-lithiostyrenes, generated by the Br/Li exchange between 1 and BuLi, with isocyanates
under the conditions previously reported by us [1].
N-(4-Chlorophenyl)-2-(1-methylethen-1-yl)benzamide (2b). White solid. M.p. 138 – 1408 (hexane/
THF). IR (KBr): 3279, 3244, 1655, 1603. 1H-NMR (500 MHz): 2.09 (s, 3 H); 5.21 (s, 1 H); 5.34 (s, 1 H);
7.28 (dd, J ¼ 7.8, 0.9, 1 H); 7.32 (d, J ¼ 8.7, 2 H); 7.40 (ddd, J ¼ 7.8, 7.3, 0.9, 1 H); 7.46 (ddd, J ¼ 7.8, 7.3, 1.4,
1 H); 7.54 (d, J ¼ 8.7, 2 H); 7.79 (dd, J ¼ 7.8, 1.4, 1 H); 7.99 (br. s, 1 H). Anal. calc. for C16H14ClNO
(271.74): C 70.72, H 5.19, N 5.15; found: C 70.65, H 5.24, N 5.19.
4-Methoxy-2-(1-methylethen-1-yl)-N-phenylbenzamide (2c). White solid. M.p. 80 – 838 (hexane/
THF). IR (KBr): 3266, 3231, 1655, 1599. 1H-NMR (500 MHz): 2.09 (s, 3 H); 3.87 (s, 3 H); 5.24 (s, 1 H);
5.35 (s, 1 H); 6.76 (d, J ¼ 2.3, 1 H); 6.91 (dd, J ¼ 8.2, 2.3, 1 H); 7.29 – 7.40 (m, 3 H); 7.57 (d, J ¼ 7.8, 2 H);
7.83 (d, J ¼ 8.2, 1 H); 8.07 (br. s, 1 H). Anal. calc. for C17H17NO2 (267.32): C 76.38, H 6.41, N 5.24; found:
C 76.26, H 6.40, N 5.17.
N-(1,1-Dimethylethyl)-4-methoxy-2-(1-methylethen-1-yl)benzamide (2d). A pale-yellow solid. M.p.
70 – 738 (hexane/CH2Cl2). IR (KBr): 3291, 1632, 1605. 1H-NMR (500 MHz): 1.41 (s, 9 H); 2.08 (d, J ¼ 0.9,
3 H); 3.83 (s, 3 H); 5.09 (d, J ¼ 0.9, 1 H); 5.22 (quint., J ¼ 0.9, 1 H); 6.15 (br. s, 1 H); 6.68 (d, J ¼ 2.7, 1 H);
6.84 (dd, J ¼ 8.7, 2.7, 1 H); 7.67 (d, J ¼ 8.7, 1 H). Anal. calc. for C15H21NO2 (247.33): C 72.84, H 8.56, N
5.66; found: C 72.59, H 8.60, N 5.42.
4,5-Dimethoxy-2-(1-methylethen-1-yl)-N-phenylbenzamide (2e). A pale-yellow solid. M.p. 125 – 1288
(hexane/CH2Cl2). IR (KBr): 3271, 3242, 1645, 1599. 1H-NMR (500 MHz): 2.09 (s, 3 H); 3.94 (s, 6 H); 5.25
(s, 1 H); 5.38 (s, 1 H); 6.72 (s, 1 H); 7.32 – 7.38 (m, 3 H); 7.43 (s, 1 H); 7.58 (d, J ¼ 7.8, 2 H); 8.19 (br. s,
1 H). Anal. calc. for C18H19NO3 (297.35): C 72.71, H 6.44, N 4.71; found: C 72.92, H 6.53, N 4.51.
N-(4-Chlorophenyl)-2-(1-phenylethen-1-yl)benzamide (5b). White solid. M.p. 140 – 1438 (hexane/
THF). IR (KBr): 3266, 3239, 1651. 1H-NMR (500 MHz): 5.45 (s, 1 H); 5.85 (s, 1 H); 7.10 (d, J ¼ 8.7, 2 H);
7.17 – 7.28 (m, 5 H); 7.42 (d, J ¼ 7.3, 1 H); 7.48 (m, 5 H); 7.80 (d, J ¼ 7.3, 1 H). Anal. calc. for C21H16ClNO
(333.81): C 75.56, H 4.83, N 4.20; found: C 75.56, H 4.73, N 4.12.
N-(4-Bromophenyl)-2-(1-phenylethen-1-yl)benzamide (5c). White solid. M.p. 150 – 1528 (hexane/
THF). IR (KBr): 3235, 3173, 1651. 1H-NMR (500 MHz): 5.44 (s, 1 H); 5.79 (s, 1 H); 7.13 (d, J ¼ 8.7, 2 H);
7.23 (s, 5 H); 7.32 (d, J ¼ 8.7, 2 H); 7.41 (d, J ¼ 7.8, 1 H); 7.47 (ddd, J ¼ 7.8, 7.3, 1.4, 1 H); 7.53 (ddd, J ¼ 7.8,
7.3, 1.4, 1 H); 7.66 (dd, J ¼ 7.8, 1.4, 1 H); 8.13 (br. s, 1 H). Anal. calc. for C21H16BrNO (378.26): C 66.68, H
4.26, N 3.70; found: C 66.50, H 4.32, N 3.82.

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Helvetica Chimica Acta – Vol. 93 (2010)
N-(4-Chlorophenyl)-2-[1-(4-methylphenyl)ethen-1-yl]benzamide (5d). White solid. M.p. 115 – 1188
(hexane/CH2Cl2). IR (KBr): 3256, 3235, 1651. 1H-NMR (500 MHz): 2.29 (s, 3 H); 5.39 (s, 1 H); 5.82 (s,
1 H); 7.04 (d, J ¼ 8.2, 2 H); 7.12 (d, J ¼ 8.2, 2 H); 7.13 (d, J ¼ 8.7, 2 H); 7.19 (d, J ¼ 8.7, 2 H); 7.40 (dd, J ¼
7.3, 1.4, 1 H); 7.48 (td, J ¼ 7.3, 1.4, 1 H); 7.54 (td, J ¼ 7.3, 1.4, 1 H); 7.61 (br. s, 1 H); 7.82 (dd, J ¼ 7.3, 1.4,
1 H). Anal. calc. for C22H18ClNO (347.84): C 75.97, H 5.22, N 4.03; found: C 75.76, H 5.33, N 3.76.
4-Methoxy-N-phenyl-2-(1-phenylethen-1-yl)benzamide (5e). White solid. M.p. 117 – 1208 (hexane/
THF). IR (KBr): 3296, 1654. 1H-NMR (500 MHz): 3.89 (s, 3 H); 5.47 (s, 1 H); 5.89 (s, 1 H); 6.90 (d, J ¼
2.7, 1 H); 7.00 (dd, J ¼ 8.7, 2.7, 1 H); 7.04 (t, J ¼ 7.3, 1 H); 7.16 – 7.27 (m, 9 H); 7.65 (br. s, 1 H); 7.85 (d, J ¼
8.7, 1 H). Anal. calc. for C22H19NO2 (329.39): C 80.22, H 5.81, N 4.25; found: C 80.06, H 5.94, N 4.05.
N-Phenyl-2-(1-phenylpropen-1-yl)benzamide (5f). A mixture of stereoisomers ((E)/(Z) ca. 6 :4). A
1
pale-yellow oil. Rf (THF/hexane 1:8) 0.40. IR (neat): 3306, 1661. H-NMR (500 MHz): 1.71 (d, J ¼ 7.3,
1.8 H); 1.91 (d, J ¼ 7.3, 1.2 H); 6.07 (q, J ¼ 7.3, 0.8 H); 6.49 (q, J ¼ 7.3, 1.2 H); 7.03 – 7.57 (m, 12.4 H); 7.65
(d, J ¼ 7.3, 0.4 H); 7.78 (br. s, 0.6 H); 8.00 (dd, J ¼ 7.8, 1.4, 0.6 H). Anal. calc. for C22H19NO (313.39): C
84.31, H 6.11, N 4.47; found: C 84.15, H 6.39, N 4.46.
2,3-Dihydro-3,3-dimethyl-2-phenyl-1H-isoindol-1-one (3a). Typical Procedure. To a stirred soln. of
2a (0.15 g, 0.65 mmol) in MeCN (5 ml) at 08 was added dropwise conc. HI (0.31 g, 1.3 mmol). The
mixture was stirred at r.t. overnight. The resulting mixture was diluted by adding Et2O (15 ml), and sat.
aq. NaHCO3 (10 ml) was added. The layers were separated, and the aq. layer was extracted with Et2O
(2 ꢁ 5 ml). The combined extracts were washed with brine, dried (Na2SO4), and concentrated by
evaporation. The residual solid was recrystallized from hexane/Et2O to give pure 3a (96 mg, 62%). White
1
solid. M.p. 188 – 1908 ([12]: 191 – 192.58). The spectroscopic data (IR and H-NMR) were identical to
those reported in [1][12].
2-(4-Chlorophenyl)-2,3-dihydro-3,3-dimethyl-1H-isoindol-1-one (3b). White solid. M.p. 115 – 1188
(hexane/Et2O). IR (KBr): 1680. 1H-NMR (400 MHz): 1.64 (s, 6 H); 7.26 – 7.32 (m, 5 H); 7.47 (dd, J ¼ 8.1,
7.0, 1 H); 7.55 (dd, J ¼ 7.7, 7.0, 1 H); 7.90 (d, J ¼ 8.1, 1 H). 13C-NMR: 27.79; 88.57; 120.68; 124.02; 125.10;
128.60; 128.71; 128.94; 129.98; 132.09; 145.35; 151.53; 158.23. MS: 271 (58, Mþ), 256 (100). Anal. calc. for
C16H14ClNO (271.74): C 70.72, H 5.19, N 5.15; found: C 70.57, H 5.25, N 4.98.
2,3-Dihydro-5-methoxy-3,3-dimethyl-2-phenyl-1H-isoindol-1-one (3c). A pale-yellow solid. M.p.
91 – 948 (hexane/CH2Cl2). IR (KBr): 1674. 1H-NMR (400 MHz): 1.62 (s, 6 H); 3.90 (s, 3 H); 6.75 (d, J ¼
2.3, 1 H); 7.00 (dd, J ¼ 8.7, 2.3, 1 H); 7.08 (tt, J ¼ 7.3, 1.4, 1 H); 7.30 – 7.35 (m, 4 H); 7.85 (d, J ¼ 8.7, 1 H).
13C-NMR: 27.74; 55.72; 87.57; 104.89; 115.42; 122.51; 123.56; 123.64; 125.49; 128.52; 146.96; 153.86;
157.76; 163.18. MS: 267 (62, Mþ), 252 (100). Anal. calc. for C17H17NO2 (267.32): C 76.38, H 6.41, N 5.24;
found: C 76.09, H 6.48, N 5.18.
2-(1,1-Dimethylethyl)-2,3-dihydro-5-methoxy-3,3-dimethyl-1H-isoindol-1-one (3d). A pale-yellow
1
oil. Rf (Et2O/hexane 1:1) 0.25. IR (neat): 1690, 1613. H-NMR (400 MHz): 1.38 (s, 9 H); 1.57 (s, 6 H);
3.86 (s, 3 H); 6.68 (d, J ¼ 2.2, 1 H); 6.89 (dd, J ¼ 8.4, 2.2, 1 H); 7.68 (d, J ¼ 8.4, 1 H). 13C-NMR: 27.86;
30.02; 53.25; 55.59; 85.89; 104.82; 114.70; 123.81; 124.98; 152.76; 155.85; 162.36. MS: 247 (69, Mþ), 191
(100). Anal. calc. for C15H21NO2 (247.33): C 72.84, H 8.56, N 5.66; found: C 72.64, H 8.54, N 5.61.
2,3-Dihydro-5,6-dimethoxy-3,3-dimethyl-2-phenyl-1H-isoindol-1-one (3e). A pale-yellow oil. Rf
(THF/hexane 1:2) 0.45. IR (neat): 1674. 1H-NMR (500 MHz): 1.62 (s, 6 H); 3.96 (s, 3 H); 3.98 (s,
3 H); 6.72 (s, 1 H); 7.09 (t, J ¼ 7.3, 1 H); 7.29 – 7.37 (m, 5 H). 13C-NMR: 27.76; 56.22; 56.28; 87.78; 102.07;
105.06; 119.56; 121.90; 123.58; 128.52; 145.30; 146.88; 150.10; 153.11; 158.31. MS: 297 (29, Mþ), 282 (100).
Anal. calc. for C18H19NO3 (297.35): C 72.71, H 6.44, N 4.71; found: C 72.52, H 6.31, N 5.00.
(E)-2,3-Dihydro-3-methyl-3-phenyl-1-(phenylimino)isobenzofuran (6a). Typical Procedure. To a
stirred soln. of 5a (0.21 g, 0.71 mmol) in MeCN at 08 was added conc. HI (0.32 g, 1.4 mmol). The mixture
was stirred for 1 h at the same temp. The precipitate was collected by filtration and recrystallized from
hexane/Et2O to give 6a (0.18 g, 86%). White solid. M.p. 173 – 1758. IR (KBr): 1659. 1H-NMR (500 MHz):
2.26 (s, 3 H); 7.34 – 7.36 (m, 2 H); 7.40 – 7.51 (m, 7 H); 7.81 (dd, J ¼ 7.8, 7.3, 1 H); 7.92 (dd, J ¼ 7.8, 7.3, 1 H);
8.08 (d, J ¼ 7.8, 2 H); 9.98 (d, J ¼ 7.8, 1 H). 13C-NMR (125 MHz): 26.30; 102.41; 122.19; 123.21; 123.93;
125.49; 129.09; 129.40; 129.47; 130.22; 130.43; 130.97; 133.35; 136.12; 137.46; 152.12; 169.64. MS: 299
(100, Mþ). Anal. calc. for C21H17NO (299.37): C 84.25, H 5.72, N 4.68; found: C 84.11, H 5.79, N 4.69.
(E)-1-[(4-Chlorophenyl)imino]-1,3-dihydro-3-methyl-3-phenylisobenzofuran (6b). A pale-yellow
1
solid. M.p. 125 – 1288 (hexane/CH2Cl2). IR (KBr): 1663. H-NMR (500 MHz): 2.24 (s, 3 H); 7.33 – 7.35

Helvetica Chimica Acta – Vol. 93 (2010)
1279
(m, 2 H); 7.43 – 7.47 (m, 5 H); 7.49 (d, J ¼ 7.8, 1 H); 7.80 (dd, J ¼ 7.8, 7.3, 1 H); 7.90 (dd, J ¼ 7.8, 7.3, 1 H);
7.92 (d, J ¼ 8.7, 2 H); 9.76 (distorted d, J ¼ 7.8, 1 H). 13C-NMR: 26.33; 102.37; 122.24; 125.33 (two
overlapped C-atoms); 125.58; 127.60; 129.48; 129.71; 130.27; 130.35; 131.08; 134.83; 136.19; 137.46;
152.16; 170.89. MS: 333 (100, Mþ). Anal. calc. for C21H16ClNO (333.81): C 75.56, H 4.83, N 4.20; found: C
75.41, H 4.91, N 4.11.
(E)-1-[(4-Bromophenyl)imino]-1,3-dihydro-3-methyl-3-phenylisobenzofuran (6c). A pale-yellow
solid. M.p. 180 – 1838 (hexane/THF). IR (KBr): 1663. 1H-NMR (500 MHz): 2.24 (s, 3 H); 7.33 – 7.35 (m,
2 H); 7.43 – 7.45 (m, 3 H); 7.49 (d, J ¼ 7.3, 1 H); 7.59 (d, J ¼ 8.7, 2 H); 7.79 (dd, J ¼ 7.8, 7.3, 1 H); 7.84 (d, J ¼
8.7, 2 H); 7.90 (t, J ¼ 7.3, 1 H); 9.70 (distorted d, J ¼ 7.8, 1 H). 13C-NMR: 26.55; 106.35; 122.66; 124.80;
124.84; 125.22; 125.44; 128.20; 128.75; 129.32; 129.50; 131.71; 132.50; 134.92; 140.98; 154.03; 169.14. MS:
377 (100, Mþ). Anal. calc. for C21H16BrNO (378.26): C 66.68, H 4.26, N 3.70; found: C 55.39, H 4.00, N
3.79.
(E)-1-[(4-Chlorophenyl)imino]-1,3-dihydro-3-methyl-3-(4-methylphenyl)isobenzofuran (6d). White
solid. M.p. 121 – 1248 (hexane/THF). IR (KBr): 1663. 1H-NMR (500 MHz): 2.23 (s, 3 H); 2.37 (s, 3 H);
7.20 (d, J ¼ 8.7, 2 H); 7.23 (d, J ¼ 8.7, 2 H); 7.43 (d, J ¼ 8.7, 2 H); 7.46 (d, J ¼ 7.8, 1 H); 7.79 (dd, J ¼ 7.8, 7.3,
1 H); 7.90 (dd, J ¼ 7.8, 7.3, 1 H); 7.92 (d, J ¼ 8.7, 2 H); 9.78 (distorted d, J ¼ 7.8, 1 H). 13C-NMR: 21.12;
26.08; 103.10; 122.25; 123.30; 125.28; 125.65; 129.63; 130.05; 130.27; 130.97; 131.99; 132.85; 134.84;
137.55; 140.77; 152.37; 169.63. MS: 347 (100, Mþ). Anal. calc. for C22H18ClNO (347.84): C 75.97, H 5.22, N
4.03; found: C 75.97, H 5.21, N 4.03.
(E)-1,3-Dihydro-5-methoxy-3-methyl-3-phenyl-1-(phenylimino)isobenzofuran (6e). A pale-yellow
solid. M.p. 146 – 1498 (hexane/THF). IR (KBr): 1668, 1603. 1H-NMR (500 MHz): 2.22 (s, 3 H); 3.96 (s,
3 H); 6.84 (d, J ¼ 2.3, 1 H); 7.26 (dd, J ¼ 8.7, 2.3, 1 H); 7.33 – 7.38 (m, 3 H); 7.42 – 7.47 (m, 5 H); 7.96 (d, J ¼
7.8, 2 H); 9.85 (d, J ¼ 8.7, 1 H). 13C-NMR: 26.13; 56.53; 100.13; 107.18; 115.31; 117.34; 117.40; 123.65;
125.43; 128.24; 129.32; 129.96; 131.72; 134.62; 136.68; 153.23; 155.53; 167.14. MS: 329 (100, Mþ). Anal.
calc. for C22H19NO2 (329.39): C 80.22, H 5.81, N 4.25; found: C 80.03, H 5.85, N 4.17.
(E)-3-Ethyl-1,3-dihydro-3-phenyl-1-(phenylimino)isobenzofuran (6f). A pale-yellow solid. M.p.
1
186 – 1898 (hexane/THF). IR (KBr): 1665. H-NMR (500 MHz): 0.85 (t, J ¼ 7.3, 3 H); 2.48 – 2.56 (m,
1 H); 2.71 – 2.78 (m, 1 H); 7.37 – 7.46 (m, 6 H); 7.51 (t, J ¼ 7.8, 2 H); 7.59 (d, J ¼ 7.8, 1 H); 7.78 (dd, J ¼ 7.8,
7.3, 1 H); 7.93 (dd, J ¼ 7.8, 7.3, 1 H); 8.02 (dd, J ¼ 7.8, 0.9, 2 H); 9.86 (d, J ¼ 7.8, 1 H). 13C-NMR: 8.11;
32.53; 105.12; 122.38; 123.87; 124.04; 125.23; 129.01; 129.38; 129.54; 129.85; 130.19; 130.90; 133.49;
136.12; 137.24; 150.47; 169.53. MS: 313 (100, Mþ). Anal. calc. for C22H19NO (313.39): C 84.31, H 6.11, N
4.47; found: C 84.07, H 6.30, N 4.47.
3-Methyl-3-phenylisobenzofuran-1(3H)-one (7) [13]. To a stirred soln. of 6a (0.71 g, 0.24 mmol) in
1,2-dimethoxyethane (DME; 3 ml) at 08 was added 10% aq. HCl (0.71 ml). The mixture was then heated
at reflux for 30 min. The cooled mixture was diluted with H2O (10 ml) and extracted with Et2O (2 ꢁ
7 ml). The combined extracts were washed with sat. aq. NH4Cl and brine, and dried (Na2SO4). After
evaporation of the solvent, the residual solid was purified by recrystallization from hexane/Et2O to give 7
1
(42 mg, 79%). White solid. M.p. 76 – 778 ([13a]: 77 – 788). The spectroscopic data (IR and H-NMR)
were identical to those reported in [13c].
We thank Mrs. Miyuki Tanmatsu of this university for recording mass spectra and performing
combustion analyses.
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Received April 29, 2010